title: An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice.
abstract: BACKGROUND
  Recent evidence indicates that the composition of the gut microbiota contributes to the development of metabolic disorders by affecting the physiology and metabolism of the host. Metformin is one of the most widely prescribed type 2 diabetes (T2D) therapeutic agents.
  
  
  OBJECTIVE
  To determine whether the antidiabetic effect of metformin is related to alterations of intestinal microbial composition.
  
  
  METHODS
  C57BL/6 mice, fed either a normal-chow diet or a high-fat diet (HFD), were treated with metformin for 6 weeks. The effect of metformin on the composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Adipose tissue inflammation was examined by flow cytometric analysis of the immune cells present in visceral adipose tissue (VAT).
  
  
  RESULTS
  Metformin treatment significantly improved the glycaemic profile of HFD-fed mice. HFD-fed mice treated with metformin showed a higher abundance of the mucin-degrading bacterium Akkermansia than HFD-fed control mice. In addition, the number of mucin-producing goblet cells was significantly increased by metformin treatment (p<0.0001). Oral administration of Akkermansia muciniphila to HFD-fed mice without metformin significantly enhanced glucose tolerance and attenuated adipose tissue inflammation by inducing Foxp3 regulatory T cells (Tregs) in the VAT.
  
  
  CONCLUSIONS
  Modulation of the gut microbiota (by an increase in the Akkermansia spp. population) may contribute to the antidiabetic effects of metformin, thereby providing a new mechanism for the therapeutic effect of metformin in patients with T2D. This suggests that pharmacological manipulation of the gut microbiota in favour of Akkermansia may be a potential treatment for T2D.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, , Seoul, Korea.
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Shin
authors.forename: June-Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Hae-Youn
authors.initials: HY
authors.lastname: Lee
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Whon
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Bae
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat; D004334:Drug Administration Schedule; D005434:Flow Cytometry; D006706:Homeostasis / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D064307:Microbiota / Q000187:drug effects*; D061327:Verrucomicrobia / Q000254:growth & development* / Q000302:isolation & purification
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Intestinal Bacteria; Mucins; Obesity; Pharmacotherapy